Oil-in-water type emulsified composition

ABSTRACT

An oil-in-water emulsion composition containing a vitamin A fatty acid ester, which further contains means for preventing oxidation of the vitamin A fatty acid ester and means for preventing hydrolysis of the vitamin A fatty acid ester. The vitamin A fatty acid ester is stabilized in the composition. The composition is particularly suitable for purposes of external-use.

DESCRIPTION

1. Technical Field

The present invention relates to an oil-in-water (O/W) emulsioncomposition which is primarily used as a composition for external use.More particularly, the present invention relates to an O/W emulsioncomposition in which a vitamin A fatty acid ester is stabilized.

2. Background Art

Vitamin A and vitamin A fatty acid esters have conventionally been knownas effective ingredients for prevention and therapy of keratinization ofthe skin and retardation of and restoration from aging of the skin.Thus, vitamin A and vitamin A fatty acid esters are incorporated into avariety of external-use compositions formulated for these purposes.

However, vitamin A and vitamin A fatty acid esters are inherently veryunstable. That is, they are easily degraded when they undergoisomerization or oxidation evoked by any of a number of factors, such aslight, air, heat, and metal ions. Therefore, external-use compositionscontaining vitamin A or vitamin A fatty acid esters exhibitunsatisfactory stability over time and in addition have drawbacks suchas need for particularly careful attention to storage conditions.

Among such unstable vitamin A and vitamin A fatty acid esters, vitamin Ahas already been a target of a variety of means for stabilization in anexternal-use composition. Among such means, use of a chelating agent anduse of an antioxidant have been proposed.

As compared with vitamin A, fatty acid esters of vitamin A exhibitexcellent stability against oxidation, and yet, due to their chemicalstructure, the fatty acid esters are prone to hydrolysis. Stabilizationmethods typified by the above methods can improve stability of vitamin Afatty acid esters against oxidation, but cannot improve stabilityagainst the problematic hydrolysis.

Accordingly, an object of the present invention is to provide means forenhancing the stability of fatty acid esters of vitamin A againsthydrolysis.

DISCLOSURE OF THE INVENTION

In an attempt to attain the above-mentioned objective, the presentinventors have carried out extensive studies in search for effectivemeans for stabilizing vitamin A fatty acid esters contained in an O/Wemulsion composition, and have found that the objective can be attainedby the provision of means for preventing oxidation of vitamin A fattyacid esters together with means for preventing hydrolysis of vitamin Afatty acid esters, thus leading to completion of the present invention.

Accordingly, the present invention provides an O/W emulsion compositioncontaining a vitamin A fatty acid ester, which composition comprisesmeans for preventing oxidation of the vitamin A fatty acid estertogether with means for preventing hydrolysis of the vitamin A fattyacid ester.

According to the present invention, the O/W emulsion composition of thepresent invention can be divided into two cases, depending on the formof the composition: essences and creams.

In the case in which the O/W emulsion composition of the presentinvention assumes the essence form, the present inventors have foundthat the aforementioned objective can be attained by incorporating anantioxidant into the oil phase of the composition and alsoincorporating, as means for preventing hydrolysis of a vitamin A fattyacid ester, a hydrophilic nonionic surfactant or nonionic amphipathicsubstance under specific conditions.

Thus, the present invention also provides an O/W emulsion compositionwhich assumes, inter alia, an essence form and which comprises means forpreventing oxidation of a vitamin A fatty acid ester and means forpreventing hydrolysis of the vitamin A fatty acid ester, wherein themeans for preventing hydrolysis of the vitamin A fatty acid estercomprises a limited amount of a hydrophilic nonionic surfactant, or, anonionic amphipathic polymer having a molecular weight of 5,000 or more.

In the case in which the O/W emulsion composition of the presentinvention assumes the cream form, the present inventors have found thatthe aforementioned objective can be attained by incorporating anantioxidant into the oil phase of the composition and alsoincorporating, as means for preventing hydrolysis of a vitamin A fattyacid ester, an amphipathic substance and a hydrophilic nonionicsurfactant under specific conditions.

Thus, the present invention also provides an O/W emulsion compositionwhich assumes, inter alia, a cream form and which comprises means forpreventing oxidation of a vitamin A fatty acid ester and means forpreventing hydrolysis of the vitamin A fatty acid ester, wherein themeans for preventing hydrolysis of the vitamin A fatty acid estercomprises an amphipathic substance and a hydrophilic nonionicsurfactant, the amphipatic substance and the hydrophilic nonionicsurfactant being incorporated into the composition under the followingconditions 1) through 3):

1) the gel transition temperature in a three-phase system consisting ofthe amphipathic substance, the hydrophilic nonionic surfactant, andwater is 50° C. or higher;

2) the ratio by weight of the amphipathic substance to the hydrophilicnonionic surfactant is 0.5 or more; and

3) the total amount of all surfactants incorporated into the compositionis 5.0% by weight or less with respect to the entirety of thecomposition.

As used herein, I.O.B. (Inorganic/Organic Balance) value serves as abasis for calculation of Σ I.O.B. value, which is a factor thatdetermines characteristics of the O/W emulsion composition of thepresent invention, and signifies an index representing the polarity ofan oily component. Briefly, I.O.B. represents the ratio of an inorganicvalue of an oily component to an organic value of the oily component[note: the ratio is calculated as follows: an organic value of 20 isassigned for each carbon atom in the molecule of the oily component, andan inorganic value of 100 is assigned per hydroxyl group in the moleculeof the oily component, and these values are used as yardsticks forcalculation of an inorganic value of another substituent (inorganicgroup); see (1) “Organic Analysis” authored by Fujita (1930), publishedby Kaniya Shoten, (2) “Prediction of Organic Compounds and OrganicConceptional Diagram (Kagaku-no-Ryoiki 11-10)” (1957), pp.719-725,authored by Fujita, (3) “Systematic Organic Qualitative Analysis (Bookof Purified Substances)” (1970), p.487, authored by Fujita and Akatsuka,published by Kazama Shoten, (4) “Organic Conceptional Diagram, ItsFundamentals and Applications” (1984), p.227, authored by Koda,published by Sankyo Shuppan, (5) “Design of Emulsion Formulations by useof Organic Conceptional Diagram” (1985), p.98, authored by Yaguchi,published by Nippon Emulsion K. K., and (6) R. H. Ewell, J. M. Harrison,L. Berg.: Ind. Eng. Chem. 36, 871 (1944)], and is expressed by:

I.O.B.=<inorganic value of the oily component>÷<organic value of theoily component>.

In the present invention, the Σ I.O.B. value is defined as a summationof I.O.B. values of respective oily ingredients which constitute the oilphase of the emulsion.

Thus, Σ I.O.B. is defined as

Σ I.O.B.=<the inorganic value of the oil phase>÷<the organic value ofthe oil phase>, wherein the inorganic value of the oil phase isexpressed by A×x+B×y+C×z+ . . . (wherein A, B, C, . . . representinorganic values, on an organic conceptional diagram, of the respectiveoily ingredients which constitute the oil phase of the emulsion and x,y, z, . . . represent proportions of respective oily ingredients A, B,C, . . . which constitute the oil phase of the emulsion, and x+y+z+ . .. =1), and the organic value of the oily phase is expressed byA′×x+B′×y+C′×z+ . . . (wherein A′, B′, C′, . . . represent organicvalues, on an organic conceptional diagram, of the respective oilyingredients which constitute the oil phase of the emulsion).

The greater the Σ I.O.B. value, the more prominent the inorganicproperties of the oil phase, indicating higher polarity.

As will be described hereinbelow, silicone oils are excluded from thecategory of the aforementioned “respective oily ingredients whichconstitute the oil phase.” Thus, when a silicone oil is present in theoil phase, the silicone oil is ignored for the purpose of calculation ofthe Σ I.O.B. value.

BEST MODES FOR CARRYING OUT THE INVENTION

Several modes for carrying out the present invention are describedbelow.

As is described above, the O/W emulsion composition of the presentinvention (hereinafter simply referred to as “the emulsion compositionof the present invention”) is particularly designed for thestabilization of a vitamin A fatty acid ester incorporated therein.

A. Vitamin A Fatty Acid Ester

As described above, the emulsion composition of the present invention isan O/W emulsion composition containing a vitamin A fatty acid ester.

Examples of the vitamin A fatty acid ester which is contained in theemulsion composition of the present invention and which is to bestabilized include vitamin A acetate, vitamin A palmitate, and vitamin Apropionate. No particular limitation is imposed on the type of theester, so long as it is vitamin A esterified by a fatty acid.

When a mixture of vitamin A fatty acid esters—for example, animal andvegetable oil containing vitamin A fatty acid esters from marine animalsor plants—is incorporated into the emulsion composition of the presentinvention, such vitamin A fatty acid esters contained in the oil arealso targets of stabilization according to the present invention.

The emulsion composition of the present invention contains a vitamin Afatty acid ester in an amount of generally not less than 0.0001 wt. %with respect to the entirety of the composition, preferably 0.001-10.0wt. %, although the amount is not particularly limited.

B. Means for Preventing Oxidation of the Vitamin A Fatty Acid Ester

As is described above, the emulsion composition of the present inventionis an O/W emulsion composition comprising means for preventing oxidationof the vitamin A fatty acid ester.

No particular limitation is imposed on the means for preventingoxidation of the vitamin A fatty acid ester, so long as the means canprevent oxidation of the vitamin A fatty acid ester in an O/W emulsion.In the present invention, there may be used antioxidants which arewidely used in external-use compositions such as cosmetic compositions.Since the vitamin A fatty acid ester is an oil-phase ingredient in theO/W emulsion, an oil-soluble antioxidant which can act directly on thevitamin A fatty acid ester for the prevention of oxidation in the oilphase is preferably and practically used.

The term “oil-soluble antioxidant” refers to an oil-soluble substancehaving anti-oxidation capability, and no particular limitation isimposed on the type of the antioxidant, so long as it can beincorporated into an external-use composition in consideration ofsafety.

Specifically, examples of oil-soluble antioxidants includebutylhydroxytoluene (hereinafter referred to as BHT), butylhydroxyanisol(hereinafter referred to as BHA), α-tocopherol, β-tocopherol,γ-tocopherol, δ-tocopherol, nordihydroguaiaretin, propyl gallate,vitamin C fatty acid esters, and sorbic acid. The emulsion compositionof the present invention may contain one or more oil-solubleantioxidants.

In order to prevent oxidation of the vitamin A fatty acid ester in theemulsion composition of the present invention, the composition containspreferably an oil-soluble antioxidant in an amount of not less than0.001 wt. % with respect to the entirety of the composition, morepreferably not less than 0.01 wt. %. The maximum amount is notparticularly limited, but the composition contains an oil-solubleantioxidant generally in an amount of not more than 10.0 wt. % withrespect to the entirety of the composition.

The emulsion composition of the present invention may containantioxidants other than those described above, including water-solubleantioxidants such as ascorbic acid, in order to prevent oxidation of thebelow-described ingredients of the composition other than the vitamin Afatty acid ester.

C. Means for Preventing Hydrolysis of the Vitamin A Fatty Acid Ester

The emulsion composition of the present invention is an O/W emulsioncomposition comprising means for preventing hydrolysis of the vitamin Afatty acid ester as well as the above-described means for preventingoxidation thereof.

The means for preventing hydrolysis of the vitamin A fatty acid ester isselected in accordance with the specific form of the emulsioncomposition of the present invention. Therefore, the means forpreventing hydrolysis depends on the form of the composition; i.e., 1)an essence form or 2) a cream form.

The term “essence form” refers to a viscous solution, and this term isnot necessarily drawn to only the limited product form of a “beautylotion.” As used herein, the expression “the emulsion composition of thepresent invention assumes an essence form” simply means that theemulsion composition of the present invention preferably assumes anessence form, and the composition may be formed into product forms otherthan beauty lotions, such as lotions, milky lotions, creams, and packs.

In addition, the term “cream form” fundamentally refers to an O/W creamform, in particular, an O/W cream form in which a gel is formed.

1. Means for Preventing Hydrolysis of the Vitamin A Fatty Acid Esterwhen the Emulsion Composition of the Present Invention is in EssenceForm

When the emulsion composition of the present invention is in essenceform, the following may further be selected as means for preventinghydrolysis of the vitamin A fatty acid ester: (1) incorporation of ahydrophilic nonionic surfactant into the composition in a limited amount(such an emulsion composition is hereinafter referred to as a “firstemulsion composition of the present invention”); and (2) incorporationof a nonionic amphipathic polymer having a molecular weight of not lessthan 5000 into the composition (such an emulsion composition ishereinafter referred to as a “second emulsion composition of the presentinvention”).

(1) Incorporation of a Hydrophilic Nonionic Surfactant into theComposition in a Limited Amount as Means for Preventing Hydrolysis ofthe Vitamin A Fatty Acid Ester (the first Emulsion Composition of thePresent Invention)

As is described above, a hydrophilic nonionic surfactant is incorporatedinto the first emulsion composition of the present invention in alimited amount as means for preventing primarily hydrolysis of thevitamin A fatty acid ester.

Examples of “hydrophilic nonionic surfactants” which may be incorporatedinto the first emulsion composition of the present invention includepolyoxyethylene (hereinafter referred to as POE) sorbitan fatty acidesters such as POE sorbitan monooleate; POE sorbitol fatty acid esterssuch as POE sorbitol monooleate; POE glycerin fatty acid esters such asPOE glyceryl monostearate and POE glyceryl monoisostearate; POE fattyacid esters such as POE monooleate, POE distearate, and POE dioleate;POE alkyl ethers such as POE oleyl ether, POE stearyl ether, POE behenylether, POE 2-octyldodecyl ether, POE 2-hexyldecyl ether, POE2-heptylundecyl ether, POE 2-decyltetradecyl ether, POE2-decylpentadecyl ether, and POE cholestanol ether; POE alkylphenylethers such as POE octylphenyl ether and POE nonylphenyl ether;pluaronics; POE·polyoxypropylene (hereinafter polyoxypropylene will bereferred to as POP) alkyl ethers such as POE·POP cetyl ether and POE·POP2-decyltetradecyl ether; POE castor oil or hydrogenated castor oilderivatives such as POE castor oil; POE beeswax or lanolin derivativessuch as POE sorbitol beeswax; polyglycerin monoalkyl esters or monoalkylethers; sucrose fatty acid esters such as sucrose monooleate; andsilicone surfactants. The first emulsion composition of the presentinvention may contain one or more hydrophilic nonionic surfactants.

The lower critical solution temperature of a hydrophilic nonionicsurfactant incorporated into the first emulsion composition of thepresent invention; i.e., a cloud point, is used as an index ofhydrophilicity of the surfactant, and the cloud point is preferably notless than 30° C., more preferably not less than 50° C., particularlypreferably not less than 70° C.

When a surfactant having a cloud point of less than 30° C. isincorporated into the composition, the surfactant may cause a decreasein stability of the vitamin A fatty acid ester in the composition, whichis unsatisfactory.

In view of the foregoing, examples of preferred hydrophilic nonionicsurfactants include POE (60) hydrogenated castor oil, POE (40) stearylether, and POE (20) oleyl ether, each of which has a cloud point of notless than 70° C.

The ratio by weight of a hydrophilic nonionic surfactant to the oilphase in the first emulsion composition of the present invention is notmore than 0.1, preferably not more than 0.05, particularly preferablynot more than 0.02.

When the weight ratio of the hydrophilic nonionic surfactant to the oilphase is more than 0.1, the surfactant forms a large number of micellesin the aqueous phase. Consequently, the micelles may cause hydrolysis ofthe vitamin A fatty acid ester, and the ester may show a strong tendencyto exhibit decreased stability, which is unsatisfactory.

When the ratio is less than 0.001, an emulsion condition in thecomposition becomes unstable, resulting in oil-floating, which isunsatisfactory.

In addition, the total amount of all surfactants incorporated into thefirst emulsion composition of the present invention including theabove-described hydrophilic nonionic surfactant is not more than 1.0 wt.% with respect to the entirety of the composition, preferably not morethan 0.5 wt. %. When the total amount of the surfactants is more than1.0 wt. %, the stability of the vitamin A fatty acid ester may decreaseaccording to composition, which is unsatisfactory.

In addition to the above-described hydrophilic nonionic surfactant, thefirst emulsion composition of the present invention may containoleophilic nonionic surfactants, in accordance with needs.

Generally, it is difficult to incorporate other types of surfactants;specifically, cationic surfactants, anionic surfactants, or amphotericsurfactants, into the first emulsion composition of the presentinvention while maintaining the intended effect of the invention.However, these surfactants may be incorporated into the composition ofthe present invention.

In the first emulsion composition of the present invention, oilyingredients are preferably selected and incorporated so as to obtain a ΣI.O.B. value of the oil phase of not less than 0.043, more preferablynot less than 0.128.

When the Σ I.O.B. value is less than 0.043, the vitamin A fatty acidester in the composition may show a tendency to exhibit decreasedstability according to composition, which is unsatisfactory.

When the Σ I.O.B. value becomes high, polarity of the entire oil phaseincreases, the vitamin A fatty acid ester hardly transfers into theaqueous phase and to an interface, and the stability of the vitamin Afatty acid ester may improve.

The first emulsion composition of the present invention may containsilicone oil as an oily ingredient. Silicone oil is irrelevant to the ΣI.O.B. value, since the oil has fundamentally no carbon atoms in themolecule. When silicone oil is incorporated into the emulsioncomposition, the oil does not adversely affect the stability of thevitamin A fatty acid ester; i.e., does not impede the intended effect ofthe present invention, and does not change the Σ I.O.B. value.

The first emulsion composition of the present invention preferablycontains the above-described oily ingredients in an amount of not lessthan 1.0 wt. % with respect to the entirety of the composition, morepreferably not less than 3.0 wt. %. When the amount is less than 1.0 wt.%, the vitamin A fatty acid ester in the composition shows a strongtendency to exhibit decreased stability, which is unsatisfactory.

Meanwhile, when the total amount of the above-described oily ingredientsis in excess of 80.0 wt. %, the composition may not maintain a stableO/W emulsion system, which is unsatisfactory.

No particular limitation is imposed on the oily ingredients incorporatedinto the first emulsion composition of the present invention, so long asthey satisfy the above-described conditions. Specifically, in the firstemulsion composition of the present invention, oily ingredients may beappropriately selected from the below-described general examples ofthose used in external-use compositions so as to satisfy theabove-described conditions.

(2) Incorporation of a Nonionic Amphipathic Polymer having a MolecularWeight of not Less than 5000 into the Composition as Means forPreventing Hydrolysis of the Vitamin A Fatty Acid Ester (the secondemulsion composition of the present invention)

The expression “a nonionic amphipathic polymer having a molecular weightof not less than 5000” incorporated into the second emulsion compositionof the present invention refers to a molecule having nonionichydrophilic and hydrophobic groups and a molecular weight of not lessthan 5000. No particular limitation is imposed on the type of polymer,so long as it can be incorporated into an external-use composition inconsideration of safety. As is described above, a nonionic amphipathicpolymer having a molecular weight of not less than 5000 is incorporatedinto the second emulsion composition of the present invention as meansfor primarily preventing hydrolysis of the vitamin A fatty acid ester.

Examples of “nonionic amphipathic polymers having a molecular weight ofnot less than 5000” which may be incorporated into the second emulsioncomposition of the present invention include partially-saponifiedpolyvinyl alcohol; cellulose polymers such as methylcellulose,ethylcellulose, methyl hydroxypropyl cellulose, hydroxyethylcellulose,and hydroxypropylcellulose; cellulose derivatives obtained from themodification of the above-described cellulose polymers by use of C₈-C₃₀alkyl groups; copolymers of polyvinylpyrrolidone and vinyl compoundshaving hydrophobic groups; polyether modified silicones such aspoly(oxyethylene-oxypropylene) methylpolysiloxane copolymer anddimethylpolysiloxane methy(polyoxyethylene)siloxane copolymer;graft-copolymers of compounds having hydrophobic groups and polyethyleneglycol; and alkylated polyoxyethylene. The second emulsion compositionof the present invention may contain one or more nonionic amphipathicpolymers having a molecular weight of not less than 5000.

The molecular weight of a nonionic amphipatic polymer which isincorporated into the second emulsion composition of the presentinvention is not less than 5000, preferably not less than 10000, morepreferably not less than 20000. When a nonionic amphipatic polymerhaving a molecular weight of less than 5000 is incorporated into thecomposition, hydrolysis of the vitamin A fatty acid ester cannot besufficiently prevented, which is unsatisfactory.

The second emulsion composition of the present invention preferablycontains a nonionic amphipathic polymer having a molecular weight of notless than 5000 in an amount of 0.01-10.0 wt. % with respect to theentirety of the composition, more preferably 0.01-3.0 wt. %,particularly preferably 0.01-1.0 wt. %. When the amount is less than0.01 wt. %, the composition may not be emulsified. When the amount is inexcess of 10.0 wt. %, the vitamin A fatty acid ester shows a strongtendency to exhibit decreased stability, and the composition cannotprovide satisfaction in use, which is unsatisfactory.

Generally, it is difficult to incorporate general surfactants;specifically, nonionic surfactants, cationic surfactants, anionicsurfactants, or amphoteric surfactants into the second emulsioncomposition of the present invention in addition to a nonionicamphipathic polymer having a molecular weight of not less than 5000,while maintaining the intended effect of the invention, sinceincorporation of general surfactants possibly impedes the intendedeffect. However, these general surfactants may be incorporated into thecomposition of the present invention.

In the second emulsion composition of the present invention, one or moreoily ingredients are preferably selected and incorporated so as toobtain a Σ I.O.B. value of the oil phase of not less than 0.043, morepreferably not less than 0.128. When the Σ I.O.B. value is less than0.043, the vitamin A fatty acid ester in the composition may show atendency to exhibit decreased stability according to composition, whichis unsatisfactory.

When the Σ I.O.B. value becomes high, polarity of the entire oil phaseincreases, and the vitamin A fatty acid ester hardly transfers into theaqueous phase and to an interface, and the stability of the vitamin Afatty acid ester can be enhanced.

The second emulsion composition of the present invention may containsilicone oil as an oily ingredient. Silicone oil is irrelevant to the ΣI.O.B. value, since the oil has fundamentally no carbon atoms in itsmolecule. When silicone oil is incorporated into the emulsioncomposition, the oil does not adversely affect the stability of avitamin A fatty acid ester; i.e., the intended effect of the presentinvention, and does not change the Σ I.O.B. value.

The second emulsion composition of the present invention preferablycontains the above-described oily ingredients in an amount of not lessthan 1.0 wt. % with respect to the entirety of the composition, morepreferably not less than 3.0 wt. %. When the amount is less than 1.0 wt.%, the vitamin A fatty acid ester in the composition shows a strongtendency to exhibit decreased stability, which is unsatisfactory.

Meanwhile, when the amount of the above-described oily ingredients is inexcess of 80.0 wt. %, the composition may not maintain a stable O/Wemulsion system, which is unsatisfactory.

No particular limitation is imposed on the oily ingredients incorporatedinto the second emulsion composition of the present invention, so longas they satisfy the above-described conditions. Specifically, in thesecond emulsion composition of the present invention, oily ingredientsmay be appropriately selected from the below-described general examplesof those used in external-use compositions so as to satisfy theabove-described conditions.

2. Means for Preventing Hydrolysis of the Vitamin A Fatty Acid Esterwhen the Emulsion Composition of the Present Invention is in a CreamForm

The emulsion composition of the present invention of the present mode(hereinafter referred to as “the third emulsion composition of thepresent invention”) is an O/W emulsion composition different from thefirst or second emulsion composition of the present invention. Thecomposition of the present mode in which a gel is formed to preventhydrolysis of the vitamin A fatty acid ester.

In the third emulsion composition of the present invention, means forpreventing hydrolysis of the vitamin A fatty acid ester comprisesincorporation of an amphipathic substance and a hydrophilic nonionicsurfactant under particular conditions.

An amphipathic substance which may be incorporated into the thirdemulsion composition of the present invention is a substance having highhydrophobicity and low surface activity as compared with a generalsurfactant. No particular limitation is imposed on the amphipathicsubstance, so long as it has the above-described properties, and, forexample, a higher aliphatic alcohol, monoglyceride, or glycerylmonoalkyl ether may be used. The third emulsion composition of thepresent invention may contain one or more amphipathic substances.

Examples of “hydrophilic nonionic surfactants” which may be incorporatedinto the third emulsion composition of the present invention include POEsorbitan fatty acid esters such as POE sorbitan monooleate; POE sorbitolfatty acid esters such as POE sorbitol monooleate; POE glycerin fattyacid esters such as POE glyceryl monostearate and POE glycerylmonoisostearate; POE fatty acid esters such as POE monooleate, POEdistearate, and POE dioleate; POE alkyl ethers such as POE oleyl ether,POE stearyl ether, POE behenyl ether, POE 2-octyldodecyl ether, POE2-hexyldecyl ether, POE 2-heptylundecyl ether, POE 2-decyltetradecylether, POE 2-decylpentadecyl ether, and POE cholestanol ether; POEalkylphenyl ethers such as POE octylphenyl ether and POE nonylphenylether; pluaronics; POE·POP alkyl ethers such as POE-POP cetyl ether andPOE·POP 2-decyltetradecyl ether; POE castor oil or hydrogenated castoroil derivatives such as POE castor oil; POE beeswax or lanolinderivatives such as POE sorbitol beeswax; polyglycerin monoalkyl estersor monoalkyl ethers; sucrose fatty acid esters such as sucrosemonooleate; and silicone surfactants. The third emulsion composition ofthe present invention may contain one or more hydrophilic nonionicsurfactants.

In the third emulsion composition of the present invention, theabove-described amphipathic substance and hydrophilic nonionicsurfactant form a gel in an amphipathic substance-hydrophilic nonionicsurfactant-water system. The system should have an appropriatecombination of these substances so as to provide a gel transitiontemperature of not less than 50° C., preferably not less than 60° C.

When the gel transition temperature is less than 50° C., the vitamin Afatty acid ester in the composition exhibits decreased stability, whichis unsatisfactory.

The weight ratio of the amphipathic substance to the hydrophilicnonionic surfactant should be not less than 0.5, preferably not lessthan 0.7, more preferably not less than 1.0.

When the ratio is less than 0.5, the vitamin A fatty acid ester in thecomposition exhibits decreased stability, which is unsatisfactory.

In addition, the total amount of surfactants which are incorporated intothe third emulsion composition of the present invention including theabove-described hydrophilic nonionic surfactant should be not more than5.0 wt. % with respect to the entirety of the composition, preferablynot more than 3.0 wt. %.

When the amount of the surfactants is more than 5.0 wt. %, the vitamin Afatty acid in the composition exhibits decreased stability, which isunsatisfactory.

In accordance with needs, the third emulsion composition of the presentinvention may contain an oleophilic nonionic surfactant in addition tothe above-described hydrophilic nonionic surfactant.

Generally, it is difficult to incorporate other types of surfactants;specifically, cationic surfactants, anionic surfactants, or amphotericsurfactants into the third emulsion composition of the present inventionwhile maintaining the intended effect of the invention. However, thesesurfactants may be incorporated into the present invention.

In the third emulsion composition of the present invention, oilyingredients are preferably selected and incorporated so as to obtain a ΣI.O.B. value of the oil phase of not less than 0.043, more preferablynot less than 0.128.

When the Σ I.O.B. value is less than 0.043, the vitamin A fatty acidester in the composition may show a tendency to exhibit decreasedstability according to composition, which is unsatisfactory.

When the Σ I.O.B. value becomes high, polarity of the entire oil phaseincreases, the vitamin A fatty acid ester hardly transfers into theaqueous phase, and the stability of the vitamin A fatty acid ester inthe oil phase may improve.

The third emulsion composition of the present invention may containsilicone oil as an oily ingredient. Silicone oil is irrelevant to the ΣI.O.B. value, since the oil has fundamentally no carbon atoms in itsmolecule. When silicone oil is incorporated into the emulsioncomposition, the oil does not adversely affect the stability of thevitamin A fatty acid ester; i.e., the intended effect of the presentinvention, and does not change the Σ I.O.B. value.

The third emulsion composition of the present invention preferablycontains the above-described oily ingredients in an amount of not lessthan 1.0 wt. % with respect to the total amount of the above-describedamphipathic substance and hydrophilic nonionic surfactant, morepreferably not less than 2.0 wt. %.

When the amount is less than 1.0 wt. %, the vitamin A fatty acid esterin the composition shows a tendency to exhibit decreased stability,which is unsatisfactory.

In the third emulsion composition of the present invention, even when arelatively large amount of a hydrophilic nonionic surfactant isincorporated, the surfactant coexist with an amphipathic substance toform a gel, resulting in reduction or elimination of the freesurfactant. The present inventors have considered that the abovephenomenon can be used as means for drastically enhancing the stabilityof the vitamin A fatty acid ester in the composition. The third emulsioncomposition of the present invention has been accomplished based on thisconsideration.

No particular limitation is imposed on oily ingredients incorporated inthe third emulsion composition of the present invention, so long as theysatisfy the above-described conditions. Specifically, in the thirdemulsion composition of the present invention, oily ingredients may beappropriately selected from the below-described general examples ofthose used in external-use compositions so as to satisfy theabove-described conditions.

D. External-Use Composition of the Present Invention

In any of its modes, the emulsion composition of the present inventionis an O/W emulsion composition which may be used primarily as anexternal-use composition such as a cosmetic composition, a drug, or aquasi-drug. When the emulsion composition of the present invention isused as an external-use composition, it will be referred to as “theexternal-use composition of the present invention.” The external-usecomposition may be represented as a first, second, or third external-usecomposition of the present invention corresponding to the respectivemodes of the present invention described above. Unless otherwise stated,the expression “external-use composition of the present invention”refers to all of the three modes.

The external-use composition of the present invention is described indetail hereinbelow.

In accordance with the specific purpose, the external-use composition ofthe present invention may contain pharmaceutically active ingredients orbase ingredients, so long as they do not impede the intended effect ofthe present invention; i.e., stabilization of the vitamin A fatty acidester in the composition.

For example, when the external-use composition of the present inventionis used as a sun-care product, the composition may contain the followingpharmaceutically active ingredients: benzoic acid ultraviolet absorberssuch as p-aminobenzoic acid; anthranilic acid ultraviolet absorbers suchas methyl anthranilate; salicylic acid ultraviolet absorbers such asoctyl salicylate, phenyl salicylate, and homomenthyl salicylate;cinnamic acid ultraviolet absorbers such as isopropylp-methoxycinnamate, octyl p-methoxycinnamate, 2-ethylhexylp-methoxycinnamate, glyceryl octanoate di-p-methoxycinnamate, and[4-bis(trimethylsiloxy)methylsilyl-3-methylbutyl]-3,4,5-trimethoxycinnamicacid ester; benzophenone ultraviolet absorbers such as2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone,2-hydroxy-4-methoxybenzophenone-5-sulfonic acid, sodium2-hydroxy-4-methoxybenzophenone-5-sulfonate; and ultraviolet absorberssuch as urocanic acid, ethyl urocanate, 2-phenyl-5-methylbenzoxazole,2-(2′-hydroxy-5′-methylphenyl)benzotriazole, and4-t-butyl-4′-methoxydibenzoylmethane.

In order to obtain a humectant effect, the external-use composition ofthe present invention may contain the following humectants: polyethyleneglycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol,hexylene glycol, glycerin, diglycerin, xylitol, maltitol, maltose,D-mannitol, starch syrup, glucose, fructose, lactose, sodium chondroitinsulfate, sodium hyaluronate, sodium adenosine phosphate, sodium lactate,bile salts, pyrrolidonecarboxylic acid, glucosamine, and cyclodextrin.

Furthermore, the external-use composition may contain aspharmaceutically active ingredients vitamins which can be used forpurposes other than antioxidants; hormones such as estradiol andethynylestradiol; amino acids such as arginine, aspartic acid, cystine,cysteine, methionine, serine, leucine, and tryptophan; anti-inflammationagents such as allantoin, azulene, and glycyrrhetinic acid; whiteningagents such as arbutin; astringents such as zinc oxide and tannic acid;refrigerants such as L-menthol and camphor; sulfur; lysozyme chloride;pyridoxine hydrochloride; and γ-oryzanol.

Furthermore, the external-use composition of the present invention maycontain extracts having a variety of pharmaceutical activity, such ashouttuynia extract, phellodendron bark extract, sweet clover extract,hypericum extract, glycyrrhiza extract, paeony root extract, saponariaextract, sponge gourd extract, cinchona extract, saxifrage extract,sophora root extract, nuphar extract, fennel extract, Primula Verisextract, Primula vulgaris extract, rose extract, rehmannia root extract,lemon extract, lithospermum root extract, aloe extract, calamus rhizomeextract, eucalyptus extract, horsetail extract, sage extract, thymeextract, green tea extract, seaweed extract, cucumber extract, cloveextract, raspberry extract, balm mint extract, ginseng exract, horsechestnut extract, peach extract, peach leaf extract, mulberry barkextract, cornflower extract, witch hazel extract, placenta extract,thymus extract, and silk extract.

Pharmaceutically active ingredients which can be incorporated into theexternal-use composition of the present invention are not limited to theabove-described pharmaceutically active ingredients. In addition, inaccordance with needs, the above-described ingredients may beincorporated into the external-use composition singly or in combinationof two or more.

In accordance with the specifically desired form and product form,generally known base ingredients may be incorporated into theexternal-use composition, so long as they do not impede the intendedeffect of the present invention. Particularly, oily ingredients shouldbe carefully incorporated.

Accordingly, the external-use composition of the present invention maycontain liquid fats and oils such as linseed oil, camellia oil,macadamia nut oil, corn oil, mink oil, olive oil, avocado oil, sasanquaoil, castor oil, safflower oil, apricot kernel oil, cinnamon oil, jojobaoil, grape seed oil, sunflower oil, almond oil, rape seed oil, sesameoil, wheat germ oil, rice germ oil, rice bran oil, cotton seed oil,soybean oil, peanut oil, tea seed oil, evening primrose oil, egg yolkoil, beef foot oil, cod liver oil, triglycerin, glyceryl trioctanoate,and glyceryl triisopalmitate; liquid or solid fats and oils such ascoconut oil, palm oil, and palm kernel oil; solid fats and oils such ascacao butter, beef tallow, mutton tallow, lard, horse fat, hydrogenatedoil, hydrogenated castor oil, Japan wax, and shea butter; and waxes suchas beeswax, candelilla wax, cotton wax, carnauba wax, bayberry wax,insect wax, spermaceti, montan wax, rice bran wax, lanolin, hydrogenatedlanolin, hard lanolin, kapok wax, sugar cane wax, jojoba wax, andshellac wax.

Furthermore, the external-use composition of the present invention maycontain ester oils, including octanoic acid esters such as cetyloctanoate, isooctanoic acid esters such as glyceryl tri-2-ethylhexanoateand pentaerythritol tetra-2-ethylhexanoate, lauric acid esters such ashexyl laurate, myristic acid esters such as isopropyl myristate andoctyldodecyl myristate, palmitic acid esters such as octy palmitate,stearic acid esters such as isocetyl stearate, isostearic acid esterssuch as isopropyl isostearate, isopalmitic esters such as octylisopalmitate, oleic acid esters such as isodecyl oleate, adipic aciddiesters such as diisopropyl adipate, sebacic acid diesters such asdiethyl sebacate, and diisostearyl malate; and hydrocarbon oils such asliquid paraffin, ozokerite, squalane, squalene, pristane(2,6,10,14-tetramethylpentadecane), paraffin, isoparaffin, ceresine,vaseline (petrolatum), microcrystalline wax.

Furthermore, the external-use composition of the present invention maycontain silicones having a linear structure, such as dimethylpolysiloxane, methylphenyl polysiloxane, and methyl hydrogenpolysiloxane; cyclic silicones such as octamethylcyclotetrasiloxane,decamethylcyclopentasiloxane, and dodecamethylcyclohexasiloxane;silicone resins having a three-dimensional network structure; andsilicones such as silicone rubber.

Furthermore, the external-use composition may contain lower alcoholssuch as methanol, ethanol, propanol, and isopropanol; and sterols suchas cholesterol, sitosterol, phytosterol, and lanosterol.

Furthermore, the external-use composition of the present invention maycontain plant polymers such as gum arabic, tragacanth gum, galactan,carob gum, guar gum, karaya gum, carrageenan, pectin, agar, quince seed(Cydonia vulgaris Pers (Rosaceae)), algae colloid (seaweed extract), andstarches (rice, corn, potato, or wheat); microorganism polymers such asdextran, succinoglucan, and pullulan; starch polymers such ascarboxymethyl starch and methylhydroxypropyl starch; animal polymerssuch as collagen, casein, albumin, and gelatin; cellulose polymers suchas methylcellulose, nitrocellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, sodium cellulose sulfate,hydroxypropylcellulose, sodium carboxymethyl cellulose, crystallinecellulose, and cellulose powder; alginate polymers such as sodiumalginate and propyleneglycol alginate; vinyl polymers such as polyvinylmethyl ether and carboxyvinylpolymer (e.g. CARBOPOL); polyoxyethylenepolymers; polyoxyethylene polyoxypropylene copolymers; acrylic polymerssuch as sodium polyacrylate, poly(ethyl acrylate), and polyacrylamide;and water-soluble polymers including inorganic water-soluble polymerssuch as polyethyleneimine, cation polymers, bentonite, magnesiumaluminum silicate, laponite, hectorite, and silicic anhydride.

The external-use composition of the present invention may also containsequestering agents such as alanine, sodium edetate, sodiumpolyphosphate, sodium metaphosphate, and phosphoric acid; and pHadjusting agents such as 2-amino-2-methyl-1-propanol,2-amino-2-methyl-1,3-propanediol, potassium hydroxide, sodium hydroxide,L-arginine, L-lysine, triethanolamine, sodium carbonate, lactic acid,citric acid, glycollic acid, succinic acid, tartaric acid, DL-malicacid, potassium carbonate, sodium bicarbonate, and ammonium bicarbonate.

The external-use composition of the present invention may also containantimicrobial agents such as benzoic acid, salicylic acid, phenol,parahydroxybenzoic acid esters or parabens, p-chloro-m-cresol,hexachlorophene, benzalkonium chloride, chlorohexdin hydrochloride,trichlorocarbanilide, photosensitive dyes, and 2-phenoxyethanol.

In accordance with needs, the external-use composition of the presentinvention may also contain appropriate perfumes or coloring agents, solong as they do not impede the intended effect of the present invention.

Base ingredients which may be incorporated into the external-usecomposition of the present invention are not limited to theabove-described base ingredients.

In accordance with formulation of the desired product form, the baseingredients may be incorporated into the external-use composition inappropriate combination.

Specific formulations of the external-use composition of the presentinvention are described below.

EXAMPLES

The present invention will next be described in more detail by way ofexamples, which should not be construed as limiting the inventionthereto.

Throughout the examples, unless otherwise stated, the amount of anincorporated ingredient represents weight % with respect to the entiretyof the product containing the ingredient.

Method for Evaluating the Stability of a Vitamin A Fatty Acid Ester

In the Examples, the percent residue of the vitamin A fatty acid esterin the product is used as an index for evaluating the stability of theester incorporated into the product. The percent residue of the ester inthe product was obtained as follows: the product containing the esterwas covered with aluminum foil for protection against light and storedat 50° C. for one month, and subsequently, the product was analyzed byhigh performance liquid chromatography, and then the amount of theremaining ester was compared with the amount of ester in the productbefore storage to thereby calculate the percent residue of the ester(%). (The thus-obtained percent residue of the ester is hereinafterreferred to as “percent residue.”).

In order to obtain percent residue, high performance liquidchromatography was performed under the following conditions.

Column: C18 column (product of Shiseido Co., Ltd.) Detection: UV 310 nm.

Mobile phase: 72% methanol/10% acetonitrile/18% ion-exchange water/0.5%acetic acid (in the case of detection of retinol acetate); 100%methanol/0.5% acetic acid (in the case of detection of retinolpalmitate)

The percent residue is preferably close to 100%, and in the presentinvention, a percent residue of 80% is regarded as a benchmark value forevaluating the stabilization of the vitamin A fatty acid ester in theproduct.

Therefore, when the percent residue is not less than 80%, the product isconsidered satisfactory, whereas when it is less than 80%, the productis considered unsatisfactory.

Method for Calculating the Σ I.O.B. Value

The Σ I.O.B. value of the oil phase in the product of each example wascalculated based on the above-described method.

A. The First Emulsion Composition of the Present Invention or the FirstExternal-Use Composition of the Present Invention

The products of the examples and the comparative examples shown in thefollowing Tables A1 and A2 were subjected to the above-describedanalysis and calculation in order to evaluate the effect of the presentinvention. The results are shown in the tables.

In order to prepare the respective products in the tables, the oil phasecomponents, which were maintained at 70° C., were added to the aqueousphase components, which were maintained at room temperature, and theresultant mixture was emulsified homogeneously by use of ahomogenization mixer and cooled to room temperature.

TABLE A1 Comparative Example Example A1 A2 A3 A4 A5 A6 A7 A8 A1 A2 A3(Oil phase) Retinol acetate 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2BHT 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 — Pentaerythritol 10.0 10.010.0 10.0 5.0 3.0 1.0 0.7 10.0 30.0 10.0 tetra-2-ethyl- hexanoate POE(20) stearyl 1.0 0.5 0.2 0.1 0.01 0.01 0.01 0.01 2.0 2.0 0.1 ether(Aqueous phase) Trisodium edetate 0.02 0.02 0.02 0.02 0.02 0.02 0.020.02 0.02 0.02 0.02 Carboxyvinylpolymer 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.30.3 0.3 0.3 KOH 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Glycerin 5.05.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Methylparaben 0.1 0.1 0.1 0.10.1 0.1 0.1 0.1 0.1 0.1 0.1 Ion-exchange water B B B B B B B B B B B ΣI.O.B. 0.353 0.353 0.353 0.353 0.353 0.353 0.353 0.353 0.353 0.353 0.353Estimation Percent residue of 82 84 86 87 86 83 82 81 73 75 68 retinolacetate (%) (50° C., one month) *B: Balance

The products of Examples A1 through A4 shown in Table A1 were comparedin terms of stability of retinol acetate serving as the vitamin A fattyacid ester, in accordance with the amount of POE (20) stearyl etherserving as a hydrophilic nonionic surfactant which is incorporatedwithin the allowable range. As is apparent from Table A1, when thesurfactant content is low, the vitamin A fatty acid ester exhibitsslightly improved stability over time.

The products of Examples A5 through A7 were compared in terms ofstability of the vitamin A fatty acid ester in accordance with theamount of pentaerythritol tetra-2-ethylhexanoate which is incorporatedas an oily ingredient within the allowable range, while a small amountof POE (20) stearyl ether serving as a hydrophilic nonionic surfactantwas incorporated within the allowable range. (In this case, thesurfactant exhibits a minimum effect on the stability of the vitamin Afatty acid ester.) As is apparent from Table A1, in the product ofExample A7, wherein the minimum amount of the oily ingredient isincorporated within the preferred range, the stability of the vitamin Afatty acid ester is close to the allowable limit.

As is also apparent from Table A1, in the product of Example A8, whereinthe amount of the oily ingredient is within the allowable range butoutside the preferred range, the stability of the vitamin A fatty acidester is closer to the allowable limit than in the cases of the productsof Examples A5 through A7.

As compared with the above-described Examples, in the products ofComparative Examples 1 and 2, the amount of the incorporated hydrophilicnonionic surfactant is outside the allowable range, and in the productof Comparative Example 3, BHT serving as an oil-soluble antioxidant isnot incorporated. As is apparent from Table A1, in all products of theComparative Examples, the stability of the vitamin A fatty acid esterover time is poor; i.e., the percent residue is less than the benchmarkvalue, 80%.

As is apparent from the above results, the first emulsion composition ofthe present invention containing ingredients within the allowable rangeexhibits the intended effect, whereas the composition containingingredients outside the allowable range does not exhibit the intendedeffect.

TABLE A2 Example A9 A10 A11 A12 (Oil phase) Retinol acetate 0.2 0.2 0.20.2 BHT 0.05 0.05 0.05 0.05 Squalane 20.0 20.0 20.0 20.0 POE (20) oleylether 0.3 — — — POE (10) oleyl ether — 0.3 — — POE (7) oleyl ether — —0.3 — POE (5) oleyl ether — — — 0.3 (Aqueous phase) Trisodium edetate0.02 0.02 0.02 0.02 Carboxyvinylpolymer 0.3 0.3 0.3 0.3 KOH 0.08 0.080.08 0.08 Glycerin 5.0 5.0 5.0 5.0 Methylparaben 0.2 0.2 0.2 0.2Ion-exchange water Balance Balance Balance Balance Cloud point 90° C.60° C. 30° C. 25° C. Σ I.O.B. 0 0 0 0 Estimation Percent residue of 9089 85 81 retinol acetate (%) (50° C., one month)

The products of Examples A9 through A12 shown in Table A2 were comparedin terms of stability of the vitamin A fatty acid ester, in accordancewith the cloud point of an incorporated hydrophilic nonionic surfactant.As is apparent from Table A2, the vitamin A fatty acid ester exhibitsimproved stability over time when a hydrophilic nonionic surfactanthaving a high cloud point is incorporated.

As is also apparent from Table A2, in the product of Example A12 whichcontains a hydrophilic nonionic surfactant having a cloud point withinthe allowable range but outside the preferred range, the stability ofthe vitamin A fatty acid ester is close to the allowable limit; i.e.,the percent residue is close to the benchmark value.

TABLE A3 Example A13 A14 A15 A16 A17 A18 A19 (Oil phase) Retinol acetate0.2 0.2 0.2 0.2 0.2 0.2 0.2 BHT 0.05 0.05 0.05 0.05 0.05 0.05 0.05Pentaerythritol — 5.0 10.0 15.0 20.0 — 20.0 tetra-2-ethyl- hexanoatesqualane 20.0 15.0 10.0 5.0 — — — Cetyl 2- — — — — — 20.0 —ethylhexanoate Glyceryl tri-2- — — — — — — 20.0 ethylhexanoate POE (60)hydrogenated 0.7 0.7 0.7 0.7 0.7 0.7 0.7 castor oil (Aqueous phase)Trisodium edetate 0.02 0.02 0.02 0.02 0.02 0.02 0.02 Carboxyvinylpolymer0.3 0.3 0.3 0.3 0.3 0.3 0.3 KOH 0.08 0.08 0.08 0.08 0.08 0.08 0.08Glycerin 5.0 5.0 5.0 5.0 5.0 5.0 5.0 Methylparaben 0.2 0.2 0.2 0.2 0.20.2 0.2 Ion-exchange water B B B B B B B Σ I.O.B. 0 0.088 0.177 0.2650.353 0.128 0.353 Estimation Percent residue of 81 84 88 92 94 85 93retinol acetate (%) (50° C., one month) B: Balance

The products of Examples A13 through A19 shown in Table A3 were studiedin terms of correlation between stability of the vitamin A fatty acidester over time and Σ I.O.B value, in accordance with composition ofingredients in the oil phase.

As is apparent from Table A3, when the Σ I.O.B value is high; i.e., whenthe oil phase of the composition has high inorganic properties andpolarity, the vitamin A fatty acid ester exhibits improved stabilityover time.

TABLE A4 Comparative Example A20 Example A21 Example A4 (Oil phase)Retinol palmitate 0.2 0.2 0.2 BHT 0.1 0.1 0.1 Pentaerythritol 20.0 — 0.8tetra-2-ethylhexanoate Di (2-ethylhexyl) — 20.0 — succinate POE (20)behenyl ether 0.2 — 0.2 Polyoxyethylene (25) polyoxypropylene glycol —0.5 — (30) (Aqueous phase) Trisodium edetate 0.02 0.02 0.02Carboxyvinylpolymer 0.3 0.3 0.3 KOH 0.1 0.1 0.1 Glycerin 5.0 5.0 5.0Methylparaben 0.1 0.1 0.1 Ion-exchange water Balance Balance Balance ΣI.O.B. 0.353 0.316 0.353 Estimation Percent residue of 90 88 35 retinolpalmitate (%) (50° C., one month)

In the products of Examples A20 and A21 and Comparative Example A4 shownin Table A4, retinol palmitate is used as a vitamin A fatty acid ester.

As is apparent from Table A4, in the products of Examples wherein allincorporated ingredients fall within the allowable ranges, the vitamin Afatty acid exhibits improved stability over time, whereas in the productof Comparative Example A4, wherein the weight ratio of POE (20) behenylether serving as a hydrophilic nonionic surfactant to pentaerythritoltetra-2-ethylhexanoate serving as an oily ingredient is 0.25, which isoutside the allowable range (i.e. 0.1), the stability of the vitamin Afatty acid ester decreases considerably.

In the first emulsion composition of the present invention, whichevervitamin A fatty acid ester is incorporated, the ester improves in termsof stability over time.

In addition, as typical modes of the first emulsion composition or thefirst external-use composition of the present invention, a beauty lotion(Example A22) and a milky lotion (Example A23) of the followingformulations were prepared in accordance with conventional methods. Thebeauty lotion and the milky lotion were subjected to the above-describedanalysis, to thereby obtain the percent residue of retinol acetate,which was not less than 80%. Therefore, the result showed that the firstemulsion composition or the first external-use composition of thepresent invention is very excellent in terms of stability of retinolacetate over time.

ingredient amount (wt. %) (Example A22) Beauty lotion (oil phase)retinol acetate 0.2 BHT 0.1 glyceryl tri-2-ethylhexanoate 5.0 cetyl2-ethylhexanoate 5.0 liquid paraffin 5.0 POE (20) behenyl ether 0.2(aqueous phase) trisodium edetate 0.02 carboxyvinylpolymer 0.3 KOH 0.1glycerin 10.0 methylparaben 0.2 ion-exchange water balance (Example A23)Milky lotion (oil phase) retinol acetate 0.2 BHT 0.1 pentaerythritoltetra-2-ethylhexanoate 10.0 di (2-ethylhexyl) succinate 10.0 POE (20)behenyl ether 0.2 behenyl alcohol 0.2 stearyl alcohol 0.1 ethylparaben0.1 butylparaben 0.1 (aqueous phase) trisodium edetate 0.02carboxyvinylpolymer 0.2 KOH 0.05 glycerin 10.0 ion-exchange waterbalance

B. The Second Emulsion Composition of the Present Invention or theSecond External-Use Composition of the Present Invention

The products of the Examples and the Comparative Examples shown in thefollowing Tables B1 and B2 were subjected to the above-describedanalysis and calculation, in order to evaluate the effect of the presentinvention. The results are shown in the tables.

In order to prepare each product in the tables, the oil phasecomponents, which were maintained at 70° C., were added to the aqueousphase components, which were maintained at room temperature, and theresultant mixture was emulsified homogeneously by use of ahomogenization mixer and cooled to room temperature.

TABLE B1 Comparative Example Example B1 B2 B3 B1 B2 (Oil phase) Retinolacetate 0.2 0.2 0.2 0.2 0.2 BHT 0.1 0.1 0.1 0.1 — Pentaerythritol 20.020.0 10.0 20.0 20.0 tetra-2-ethyl- hexanoate PVA EG-05 5.0 — — — —NATROSOL — 3.0 — — — Plus330 Poly(oxyethylene · — — 1.0 — —oxypropylene) methylpolysiloxane copolymer POE (20) stearyl — — — 5.0 —ether POE (60) — — — — 5.0 hydrogenated castor oil (Aqueous phase)Trisodium edetate 0.02 0.02 0.02 0.02 0.02 Carboxyvinyl- 0.3 0.3 0.3 0.30.3 polymer KOH 0.1 0.1 0.1 0.1 0.1 Glycerin 5.0 5.0 5.0 5.0 5.0Methylparaben 0.1 0.1 0.1 0.1 0.1 Ion-exchange water Balance BalanceBalance Balance Balance Σ I.O.B. value 0.353 0.353 0.353 0.353 0.353Percent residue of 92 95 91 58 52 retinol acetate (%) Estimation PassedPassed Passed Not Not passed passed

In the products of Examples B1 through B3 shown in Table B1, within theallowable range, there is incorporated, as a nonionic amphipathicpolymer having a molecular weight of not less than 5000, PVA EG-05(product of The Nippon Synthetic Chemical Industry Co., Ltd., MW:30,000), NATROSOL Plus330 (product of Hercules, MW: 1,500,000), orpoly(oxyethylene.oxypropylene) methylpolysiloxane copolymer (MW:50,000). In contrast, in the product of Comparative Example B1,polyoxyethylene (referred to as POE in the table) (20) stearyl etherserving as a nonionic surfactant is incorporated in lieu of the nonionicamphipathic polymer, and in the product of Comparative Example B2,polyoxyethylene (referred to as POE in the table) (60) hydrogenatedcastor oil serving as a nonionic surfactant is incorporated, but BHTserving as an oil-soluble antioxidant is not incorporated.

As is apparent from Table B1, the products of Examples B1 through B3,each of which contains a nonionic amphipathic polymer having a molecularweight of not less than 5000, are superior to the products ofComparative Examples B1 and B2 in terms of stability over time ofretinol acetate serving as a vitamin A fatty acid ester.

TABLE B2 Example B4 B5 B6 B7 B8 B9 B10 (Oil phase) Retinol acetate 0.20.2 0.2 0.2 0.2 0.2 0.2 BHT 0.05 0.05 0.05 0.05 0.05 0.05 0.05Pentaerythritol — 5.0 10.0 15.0 20.0 — — tetra-2-ethyl- hexanoateSqualane 20.0 15.0 10.0 5.0 — — — Cetyl 2-ethyl- — — — — — 20.0 —hexanoate Glycerin tri(2- — — — — — — 20.0 ethylhexanoate) NATROSOLPlus330 3.0 3.0 3.0 3.0 3.0 3.0 3.0 (Aqueous phase) Trisodium 0.02 0.020.02 0.02 0.02 0.02 0.02 edetate Carboxyvinyl- 0.3 0.3 0.3 0.3 0.3 0.30.3 polymer KOH 0.08 0.08 0.08 0.08 0.08 0.08 0.08 Glycerin 5.0 5.0 5.05.0 5.0 5.0 5.0 Methylparaben 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Ion-exchange BB B B B B B water Σ I.O.B. value 0.0 0.104 0.197 0.279 0.353 0.128 0.353Percent 84 86 90 93 95 87 94 residue of retinol acetate (%) Estimation PP P P P P P B: Balance, P: Passed

The products of Examples B4 through B10 shown in Table B2 were studiedin terms of correlation between stability of the vitamin A fatty acidester over time and Σ I.O.B value, in accordance with composition ofingredients in the oil phase.

As is apparent from Table B2, when the Σ I.O.B value is high; i.e., whenthe oil phase of the composition has high inorganic properties andpolarity, the vitamin A fatty acid ester exhibits improved stabilityover time.

TABLE B3 Comparative Example B11 Example B3 (Oil phase) Retinolpalmitate 0.2 0.2 BHT 0.1 0.1 Pentaerythritol tetra-2-ethyl- 20.0 20.0hexanoate Poly (oxyethylene · oxypropylene) 5.0 — methylpolysiloxanecopolymer POE (20) stearyl ether — 5.0 (Aqueous phase) Trisodium edetate0.02 0.02 Carboxyvinylpolymer 0.3 0.3 KOH 0.1 0.1 Glycerin 5.0 5.0Methylparaben 0.1 0.1 Ion-exchange water Balance Balance Σ I.O.B. value0.353 0.353 Percent residue of 97 75 retinol palmitate (%) EstimationPassed Not passed

In the products of Example Bll and Comparative Example B3 shown in TableB3, retinol palmitate was incorporated as a vitamin A fatty acid ester.As is apparent from Table B3, whichever vitamin A fatty acid ester isincorporated, the second emulsion composition or the second external-usecomposition of the present invention exhibits improved stability of theester over time.

C. The Third Emulsion Composition of the Present Invention or the ThirdExternal-Use Composition of the Present Invention

TABLE C1 Example Comparative Example C1 C2 C3 C4 C5 C6 C7 C8 C9 C1 C2 C3C4 (Oil phase) Retinol acetate 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.2 0.20.2 0.2 0.2 BHT 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1Pentaerythritol 20.0 20.0 20.0 10.0 10.0 8.0 16.0 3.0 5.0 20.0 20.0 20.020.0 Tetra-2-ethyl- hexanoate Behenyl alcohol 1.5 2.1 3.0 7.5 7.5 — —6.0 — 1.8 — 2.0 — Stearyl alcohol — — — — — 5.0 5.0 — 5.0 — — — — Cetylalcohol — — — — — — — — — — 4.0 — 6.0 Myristyl alcohol — — — — — — — — —— — — 1.5 Ethylparaben 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.10.1 Butylparaben 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1(Aqueous phase) Trisodium edetate 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.10.1 0.1 0.1 0.1 Glycerin 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.0 5.05.0 POE (20) behenyl 3.0 3.0 3.0 — — — — 3.0 — 4.0 — 10.0 — ether POE(20) stearyl — — — 5.0 3.0 3.0 3.0 — 3.0 — — — — ether POE (15) oleyl —— — — — — — — — — 10.0 — 3.0 ether Ion-exchange water B B B B B B B B BB B B B Σ I.O.B. 0.344 0.340 0.337 0.299 0.299 0.325 0.335 0.269 0.3160.343 0.346 0.342 0.345 Estimation Percent residue of 83 86 88 81 83 8185 81 80 72 40 35 73 retinol acetate (%) (50° C., one month) B: Balance

The products of Examples C1 through C3 and Comparative Example C1 shownin Table C1 were compared in terms of the weight ratio of an amphipathicsubstance to a hydrophilic nonionic surfactant.

As is apparent from Table C1, in the products of Examples C1 through C3,wherein the ratio falls within the allowable range (i.e. not less than0.5), retinol acetate serving as a vitamin A fatty acid ester isstabilized over time, whereas in the product of Comparative Example C1,wherein the ratio is 0.45, the stability of the ester is poor; i.e., thepercent residue is less than 80% (the benchmark value).

The products of Examples C4 and C5 and Comparative Examples C2 and C3were compared in terms of the amount of the incorporated surfactant.

As is apparent from Table C1, the products of Examples C4 and C5,wherein the amount falls within the allowable range (i.e., not more than5.0 wt. % with respect to the entirety of the composition), exhibitimproved stability of the vitamin A fatty acid ester over time, whereasin the products of Comparative Examples C2 and C3, wherein the amount isoutside the range, the stability is decreased drastically.

The products of Examples C6 through C9 were compared in terms of theamount of incorporated oily ingredients.

As is apparent from the Table C1, the products of Examples C6 and C7,wherein the amount falls within the preferred range (i.e. the weightratio to the total amount of an amphipathic substance and a hydrophilicnonionic surfactant is not less than 1.0), are good in terms ofstability of the vitamin A fatty acid ester over time, whereas in thecompositions of Examples C8 and C9, wherein the amount is outside thepreferred range, the percent residue of the ester is close to thebenchmark value (80%).

The product of Comparative Example C4 contains a formulation of anamphipatic substance-hydrophilic nonionic surfactant-water system, inorder to obtain a gel transition temperature of less than 50° C.

As is apparent from Table C1, in the product of Comparative Example C4containing the system having a gel transition temperature of less than50° C., the percent residue of the vitamin A fatty acid ester is lessthan the benchmark value (80%).

TABLE C2 Example C10 C11 C12 C13 C14 (Oil phase) Retinol acetate 0.2 0.20.2 0.2 0.2 BHT 0.1 0.1 0.1 0.1 0.1 Pentaerythritol — 5.0 10.0 15.0 20.0tetra-2-ethyl- hexanoate Squalane 20.0 15.0 10.0 5.0 — Behenyl alcohol4.0 4.0 4.0 4.0 4.0 Ethylparaben 0.1 0.1 0.1 0.1 0.1 Butylparaben 0.10.1 0.1 0.1 0.1 (Aqueous phase) Trisodium edetate 0.1 0.1 0.1 0.1 0.1Glycerin 5.0 5.0 5.0 5.0 5.0 POE (20) behenyl ether 0.5 0.5 0.5 0.5 0.5Ion-exchange water Balance Balance Balance Balance Balance Σ I.O.B.0.039 0.113 0.187 0.261 0.332 Estimation Percent residue of 83 87 90 9597 retinol acetate (%) (50° C., one month)

The products of Examples C10 through C14 shown in Table C2 were comparedin terms of stability of the vitamin A fatty acid ester in accordancewith composition of the ingredients, with the Σ I.O.B. value serving asan index.

As is apparent from Table C2, when the Σ I.O.B value is high; i.e., whenthe oil phase of the composition has high inorganic properties andpolarity, the composition exhibits improved stability of the vitamin Afatty acid ester over time.

TABLE C3 Example Comparative Example C15 C16 C17 C5 C6 C7 C8 (Oil phase)Retinol palmitate 0.2 0.2 0.2 0.2 0.2 0.2 0.2 BHT 0.1 0.1 0.1 0.1 0.10.1 0.1 Pentaerythritol 20.0 — 10.0 20.0 — — — tetra-2-ethyl- hexanoateDi(2-ethylhexyl) — 10.0 5.0 — 20.0 3.0 20.0 succinate Liquid paraffin —— 5.0 — — — — Stearyl alcohol 4.0 4..0 4.0 4.0 1.8 4.0 4.0 Ethylparaben0.1 0.1 0.1 0.1 0.1 0.1 0.1 Butylparaben 0.1 0.1 0.1 0.1 0.1 0.1 0.1(Aqueous phase) Trisodium edetate 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Glycerin5.0 5.0 5.0 5.0 5.0 5.0 5.0 POE (20) oleyl 2.0 1.0 2.0 10.0 4.0 2.0 2.0ether Ion-exchange water B B B B B B B Σ I.O.B. 0.340 0.305 0.262 0.3400.347 0.310 0.340 Estimation Percent residue of 92 88 85 45 75 38 33retinol palmitate (%) (50° C., one month) B: Balance

In the products of Examples C15 through C17 and Comparative Examples C5through C8 shown in Table C3, retinol palmitate was incorporated, inorder to verify that the same results as the above-described Examplesand Comparative Examples are obtained when a different vitamin A fattyacid ester is incorporated.

As is apparent from Table C3, whichever vitamin A fatty acid ester isincorporated, the third emulsion composition or the third external-usecomposition of the present invention exhibits improved stability of theester over time.

Industrial Applicability

As is described above, the present invention provides an emulsioncomposition which contains a vitamin A fatty acid ester in a stabilizedstate and which is particularly useful as an external-use composition.

What is claimed is:
 1. An oil-in-water emulsion composition comprising:at least 0.0001 wt % vitamin A fatty acid ester; at least 0.001 wt % ofan oil-soluble antioxidant for preventing oxidation of the vitamin Afatty acid ester; and a limited amount of a hydrophilic nonionicsurfactant for preventing hydrolysis of the vitamin A fatty acid ester,wherein the oil phase of the oil-in-water emulsion composition has a ΣI.O.B. value of not less than 0.043.
 2. An oil-in-water emulsioncomposition comprising: at least 0.0001 wt. % vitamin A fatty acidester; at least 0.001 wt. % of an oil-soluble antioxidant for preventingoxidation of the vitamin A fatty acid ester; and a nonionic amphipathicpolymer having a molecular weight of 5,000 or more for preventinghydrolysis of the vitamin A fatty acid ester, wherein the oil phase ofthe oil-in-water emulsion composition has a Σ I.O.B. value of not lessthan 0.043.
 3. The oil-in-water emulsion composition according to claim1 wherein the ratio by weight of the hydrophilic nonionic surfactant tothe oil phase of the oil-in-water emulsion composition is not more than0.1, and the total amount of all surfactants incorporated into thecomposition is not more than 1.0 wt. % with respect to the entirety ofthe composition.
 4. The oil-in-water emulsion composition according toclaim 1, wherein the hydrophilic nonionic surfactant is at least onehydrophilic nonionic surfactant having a cloud point of 30° C. or more.5. The oil-in-water emulsion composition according to claim 1, whereinthe total amount of oily ingredients contained in the composition is notless then 1.0 wt. % with respect to the entirety of the composition. 6.The oil-in-water emulsion composition according to claim 2, wherein thetotal amount of oily ingredients contained in the composition is notless than 1.0 wt. % with respect to the entirety of the composition. 7.The oil-in-water emulsion composition according to claim 1, whichassumes an essence form.
 8. An oil-in-water emulsion compositioncomprising: at least 0.0001 wt. % of vitamin A fatty acid ester; atleast 0.001 wt. % of an oil-soluble antioxidant for preventing oxidationof the vitamin A fatty acid ester; and an amphipathic substance and thehydrophilic nonionic surfactant being incorporated into the compositionunder the following conditions 1) through 3): 1) the gel transitiontemperature in a three-phase system consisting of the amphipathicsubstance, the hydrophilic nonionic surfactant, and water is 50° C. orhigher; 2) the ratio by weight of the amDhipathic substance to thehydrophilic nonionic surfactant is 0.5 or more; and 3) the total amountof all surfactants incorporated into the composition is 5.0% by weightor less with respect to the entirety of the composition, for preventinghydrolysis of the vitamin A fatty acid ester.
 9. The oil-in-wateremulsion composition according to claim 8, wherein the weight ratio ofthe entirety of the oily ingredients contained in the composition to thetotal amount of the amphipathic substance and the hydrophilic nonionicsurfactant is not less than 1.0.
 10. The oil-in-water emulsioncomposition according to claim 8, which assumes a cream form.
 11. Theoil-in-water emulsion composition according to claim 8, wherein the oilphase of the oil-in-water emulsion composition has a Σ I.O.B. value ofnot less than 0.043.
 12. The oil-in-water emulsion composition accordingto claim 1, which is a composition for external use.
 13. Theoil-in-water emulsion composition according to claim 2, which is acomposition for external use.
 14. The oil-in-water emulsion compositionaccording to claim 8, which is a composition for external use.
 15. Theoil-in-water emulsion composition according to claim 2, wherein theamount of the nonionic amphipathic polymer having a molecular weight of5,000 or more is 0.01-10.0 wt. % with respect to the entirety of thecomposition.
 16. The oil-in-water emulsion composition according toclaim 2, which assumes an essence form.